Aging per se Increases the Susceptibility to Free Fatty Acid–Induced Insulin Resistance

Elevations in systemic free fatty acids (FFA) contribute to insulin resistance. To determine the effects of an acute elevation in FFA on insulin action with aging, we infused saline or intralipid (IL) during a hyperinsulinemic–euglycemic clamp in three groups of rats: young ad libitum–fed (YAL), old...

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Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2010-08, Vol.65A (8), p.800-808
Main Authors: Einstein, Francine H., Huffman, Derek M., Fishman, Sigal, Jerschow, Elina, Heo, Hye J., Atzmon, Gil, Schechter, Clyde, Barzilai, Nir, Muzumdar, Radhika H.
Format: Article
Language:English
Subjects:
Adipokines
Aging
Aging - metabolism
Animals
Caloric Restriction
Calorie restriction
Fat Emulsions, Intravenous - toxicity
Fatty acids
Fatty Acids, Nonesterified - toxicity
Gene expression
Gerontology
Glucose - metabolism
Hyperglycemia
Inflammation - metabolism
Insulin Resistance
Interleukin-6 - genetics
Journal of Gerontology: BIOLOGICAL SCIENCES
Lipids
Macrophages - physiology
Plasminogen Activator Inhibitor 1 - genetics
Rats
Rats, Inbred F344
Rodents
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Summary:Elevations in systemic free fatty acids (FFA) contribute to insulin resistance. To determine the effects of an acute elevation in FFA on insulin action with aging, we infused saline or intralipid (IL) during a hyperinsulinemic–euglycemic clamp in three groups of rats: young ad libitum–fed (YAL), old ad libitum–fed (OAL), and old on lifelong calorie restriction (OCR). The OCR group was included to distinguish between aging per se and age-related changes in body fat distribution. IL induced marked insulin resistance in both YAL and OCR, but the onset of insulin resistance was approximately two to three times more rapid in OCR as compared with YAL. In response to IL infusion, plasminogen-activating inhibitor-1 (PAI-1) expression was increased in subcutaneous fat from OAL animals. In visceral fat, a marked increase in PAI-1 and interleukin-6 expression was observed in OAL and OCR rats, but not YAL, in response to IL treatment. Thus, aging per se increases the inflammatory response to excess nutrients and vulnerability to FFA-induced insulin resistance with aging.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glq078